Proximal Resection Margin in Ivor-Lewis Oesophagectomy for Cancer.

OBJECTIVE: The purpose of this study was to investigate whether a long proximal oesophageal resection margin (PRM) is associated with improved survival after oesophagectomy for cancer and to identify the optimal margin to aim for in this patient group. METHODS: A prospectively maintained database identified 174 patients who underwent Ivor-Lewis oesophagectomy for cancer. Demographic, clinical, and pathological data were collected. X-tile software was used to identify the optimal resection point. Two models were analysed: single point resection with comparison of two groups (short and long), and two resection points with three groups (short, medium, and long) to provide a range. RESULTS: The median PRM was 4.0 cm (interquartile range: 2.5-6.0 cm). After adjustment for significant confounders, multivariable Cox PH analysis demonstrated that the optimal resection margin was 1.7 cm, and in the three-group analysis the optimum PRM was between 1.7 and 3 cm. In the two-group analysis, the long margin had no effect on DFS (p = 0.37), but carried a significantly improved overall survival (hazard ratio [HR] = 0.46, 95 % confidence interval [CI] 0.25-0.87, p = 0.02). In the three-group analysis, the medium and long groups had improved OS compared with the short group (on average 54 %, HR ≥ 0.45, p ≤ 0.04). The 5-year disease-free and overall survival rates were highest in the medium PRM group (48 and 57 % respectively). CONCLUSIONS: Optimal survival following oesophagectomy for cancer is achieved with a PRM > 1.7 cm, but a PRM > 3 cm does not yield a further survival advantage. Thus, the optimal PRM is likely to be between 1.7 and 3 cm.

Interleukin-17 Expression in the Barrett's Metaplasia-Dysplasia-Adenocarcinoma Sequence.

Introduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett's metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty (n = 40) formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where P ≤ 0.001, in IL-17 expression (Kruskall Wallis and Mann-Whitney U) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression (r s = 0.883, P < 0.001, n = 29), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma.

Fungal ball of the oesophagus.

Candidal colonization of the gastrointestinal tract is common, but localized complications are rare. A case of an oesophageal fungal ball is described.

Continent colonic conduit for the treatment of faecal incontinence associated with disordered evacuation.

A transverse colonic conduit incorporating an intussusception valve and skin-flapped cutaneous aperture was constructed in nine patients with combined faecal incontinence and disordered evacuation. Intestinal continuity was restored with a colocolonic anastomosis. Median follow-up was 4 (range 2-15) months and daily irrigation with a median of 1.2 (range 0.3-2.0) litres of water resulted in evacuation in less than 1 h. At 1 month after operation there was no leakage of solid or liquid faeces from the anus between irrigations. The valve was continent to faeces and irrigation fluid, and no stoma appliances were required.

Electrically stimulated colonic reservoir for total anorectal reconstruction.

Total anorectal reconstruction after abdominoperineal excision of the rectum has failed to achieve perfect continence. Electrically stimulated reservoir evacuation in combination with an electrically stimulated gracilis neoanal sphincter might improve results. A J pouch was constructed in an isolated colonic loop of seven dogs. Bipolar square wave pulses were delivered via two intramural stainless steel electrode pairs at 10 Hz. Stimulation parameters were varied to achieve adequate contraction. Serosal strain gauges recorded spontaneous and stimulated pouch motility. Evacuation was quantified by a volume displacement technique and observed fluoroscopically. Recordings were performed for a median of 3 (range 1-11) months. At 10 Hz and 0.5 ms pulse width, stimulation was required for 2 min and at voltages of 15 V (n = 4), 18 V (n = 1) and 20 V (n = 2) to obtain a contraction of amplitude comparable to that of a spontaneous contraction. Suprathreshold stimulation invariably resulted in colonic pouch contraction. The mean(95 per cent confidence interval (c.i.)) stimulus-response latency was 25.5(1.9) s. The mean(95 per cent c.i.) intraluminal pressure generated during stimulation was 114.1(17.0) cmH2O and 64.6(12.0) cmH2O during spontaneous activity (P < 0.001). In conclusion, electrical stimulation via intramural electrodes produced contraction generating sufficient intraluminal pressure to effect evacuation of a canine colonic pouch. This has potential for incorporation with an electrically stimulated neoanal sphincter in total anorectal reconstruction to improve evacuation and continence.

The lack of effect of tumor necrosis factor-alpha, interleukin-1-alpha, and interferon-gamma on human sperm motility in vitro.

Whether cytokines present in human peritoneal fluid reduce sperm motility, and thus contribute to infertility, is investigated. The human recombinant cytokines, tumor necrosis factor-alpha, interleukin-1-alpha, and interferon-gamma, were incubated with motile human sperm obtained from fertile men and separated by the swim-up technique. These cytokines, alone or in combination, in higher doses than those observed in vivo (greater than or equal to 25,000 U/ml), did not alter the percentage of motile sperm after 90 minutes, 24 hours, and 48 hours under standard culture conditions. Similarly, penetration of a column of bovine cervical mucus was unchanged after preincubation of the sperm with individual cytokines or combinations of several cytokines for 24 hours. In contrast to those given in previous reports, these dta do not support a direct effect of tumor necrosis factor-alpha, interleukin-1-alpha, or interferon-gamma on sperm motility, and suggest that other soluble factors are responsible for the observed effects of peritoneal fluid on sperm motility in vitro.

Thorn-induced granuloma of the medial cuneiform.

A lytic lesion of the medial cuneiform of a 10-year-old boy was explored surgically, and a date palm thorn was identified. Histology revealed an aseptic granuloma. Even in the absence of a definite history of trauma, an organic foreign body lesion should be considered in the differential diagnosis of a lytic lesion of bone.

Use of human cumulus granulosa cells for in vitro screening of reproductive toxicants.

We investigated the possibility that human granulosa cells from the cumulus mass obtained during human in vitro fertilization/embryo transfer (IVF/ET) might be useful for screening of potential reproductive toxicants in vitro. The cumulus granulosa cells detached from the zona pellucida after fertilization were allowed to spontaneously adhere to the incubation dish following transfer (removal) of the embryo. These cumulus cells survived in culture for at least four additional days, appeared on simple inspection to be morphologically normal luteinized granulosa cells, and produced large amounts of progesterone (P) over the culture interval. Production gradually declined during culture in the absence of human chorionic gonadotropin (hCG); however, inclusion of hCG (100 ng/mL) in the medium maintained P production at control (day 1) levels. Introduction of estrogenic agents previously shown to suppress P production in porcine or human culture systems using mural granulosa cells showed comparable effects in this human cumulus cell system. 17 beta-estradiol (10(-5) M), clomiphene citrate (10(-5) M), and o,p-DDT (10(-5)) significantly inhibited hCG-supported P production by human cumulus cells in vitro. This system has the advantages that (1) human cumulus granulosa cells are readily available from IVF/ET programs, (2) the techniques for maintaining the cells in culture are extremely simple, (3) a marker of highly differentiated granulosa cell function (P production) can be reliably measured, and (4) the cells respond predictably like other comparable granulosa cell systems. We conclude that human cumulus cells are a readily available and useful resource for in vitro screening of potential female reproductive toxicants.

Synthetic estrogens suppress granulosa cell progesterone production in vitro.

We evaluated the effect of commonly used pharmaceutical estrogens and zeranol, an estrogenic growth-promoting agent used in livestock, on progesterone (P) production by cultures of highly differentiated porcine granulosa cells (GC). The compounds were added to GC cultures over a dose range of 10(-8) to 10(-5) M with P and cell protein measured after 24 h. P production was suppressed by estradiol (minimal suppressive dose: 10(-7) M; maximal suppression to 11% of control), ethinyl estradiol (10(-7) M, 15%), diethylstilbestrol (10(-5) M, 72%), clomiphene citrate (10(-6) M, 30%), nafoxidine (10(-7) M, 33%), tamoxifen (10(-6) M, 37%), and zeranol (10(-5) M, 83%). P production was not suppressed by mestranol. GC protein was suppressed by estradiol, ethinyl estradiol, nafoxidine, and zeranol. These data suggest that synthetic estrogens have the potential to suppress luteal P production by a mechanism unrelated to the usual measures of estrogenicity.

Effects of acetaminophen and nonsteroidal anti-inflammatory drugs on progesterone production by porcine granulosa cells in vitro.

We investigated the effects of a group of pharmaceutical agents commonly ingested by reproductive-aged women, acetaminophen and the nonsteroidal anti-inflammatory drugs (NSAID), on progesterone (P) production by cultures of highly differentiated porcine granulosa cells. These compounds were added to cultures over a dose range of 10(-8) to 10(-5) M and P, and cell protein was measured after 24 hours. P production was suppressed by acetaminophen, fenoprofen, and sulindac to a maximum of 81%, 76%, and 71% of control, respectively. P production was enhanced by butazolidin at all doses tested to a maximum of 140% of control. Granulosa cell protein was suppressed by butazolidin and salicylic acid to a maximum of 81% of controls. These data imply that acetaminophen and several NSAID have the potential for clinical reproductive toxicity with differing individual effects on reproductive tract tissues, suggesting further selective testing in vivo.

Screening of potential reproductive toxicants by use of porcine granulosa cell cultures.

While approximately 60 000 chemicals are in widespread use with 1000 new chemicals introduced into the environment each year, the biologic effects of these agents are poorly understood. With the specific goal of testing for potential reproductive toxicity, we have established methodology for the screening of compounds in vitro by measuring effects on progesterone production by porcine granulosa cells in culture. Granulosa cells were harvested by mechanical agitation, cryopreserved, and cells with known progesterone production capacity utilized for culture. Agents to be tested were added to cultures of 10(5) cells and the media assayed for progesterone by radioimmunoassay. Estradiol suppression of progesterone production was easily demonstrated in this system and utilized as a verification of responsiveness. The pesticide o,p-DDT and its isomer p,p-DDT produced dramatic suppression of progesterone production apparently with equal potencies to estradiol. By contrast, the pesticides malathion, parathion and dieldrin and the fungicide hexachlorobenzene were without effect in this test system.